Effects of Gene-Eden-VIR and Novirin on SARS-CoV: Implications for COVID-19

Abstract

The coronavirus (SARS-CoV-2), which causes COVID-19, is a betacoronavirus closely related to the human severe acute respiratory syndrome (SARS)-coronavirus (SARS-CoV). The recent COVID-19 outbreak created an urgent need for treatment. To expedite the development of such treatment, pharmaceutical companies and government agencies are currently testing several existing drugs for their effect on the virus. Gene-Eden-VIR and Novirin are natural, broad-spectrum, antiviral treatments proven to be safe and effective in several clinical studies. In this article, we present evidence indicating that the 5 Gene-Eden-VIR/Novirin ingredients have anti-betacoronavirus, and specifically, anti-SARS-CoV effects. We consider this evidence as a first indication of the anti-coronavirus effects of Gene-Eden-VIR/Novirin. Next, we are planning to conduct a clinical study with users of the treatments to test the effects of Gene-Eden-VIR/Novirin on individuals at risk and those infected with the virus.

A novel coronavirus (SARS-CoV-2), which causes COVID-19, emerged in December 2019 in Wuhan city in China. The virus’s most recently estimated reproductive number is 2.24 ¹ to 4.08 ² R₀, and its fatality rate is 3.4%. ³ Samples collected from patients revealed that the SARS-CoV-2 is a betacoronavirus, most closely related to a bat CoV (RaTG13) with 96% identity, ^4,5 and 2 other bat-derived Severe Acute Respiratory Syndrome (SARS)-like coronaviruses (SL-CoVZC45 and SL-CoVZXC21), with 88% identity. ⁶ In addition, further analysis showed that SARS-CoV-2 is also closely related to the human SARS-CoV, with 79% identity. ^4,6 The later has an almost identical main protease (3CLpro) amino acid sequence to the SARS-CoV-2 with 96% identity and 99% similarity. ⁷

To expedite the development of a treatment, pharmaceutical companies and government agencies are currently testing several existing drugs for their effect on the SARS-CoV-2 virus. For instance, a study reported that a combination of lopinavir and ritonavir, 2 HIV protease inhibitors, which were effective against a SARS infection in patients, ⁸ reduced the viral load in a single SARS-CoV-2 infected patient. ⁹ Another study showed that 2 compounds, remdesivir, a broad-spectrum antiviral drug, which was found to be effective against betacoronaviruses in vitro and in vivo, and chloroquine, an antimalarial drug, blocked a SARS-CoV-2 infection in vitro at low concentrations and high selectivity index (remdesivir, IC₅₀ = 0.77 μM, SI > 129; chloroquine, IC₅₀ = 1.13 μM, SI > 88). Remdesivir was also effective in one SARS-CoV-2 infected patient, and it is currently tested in Chinese patients as a treatment for COVID-19. Early clinical trials performed in China demonstrated the efficacy of chloroquine in the treatment of COVID-19. ¹⁰

Gene-Eden-VIR/Novirin is a natural, broad-spectrum, antiviral treatment. The formula includes 5 ingredients: a 100 mg extract of quercetin, a 150 mg extract of green tea, a 50 mg extract of cinnamon, a 25 mg extract of licorice, and 100 µg of selenium. Clinical studies showed that Gene-Eden-VIR/Novirin is a safe and effective treatment against several viruses, including the human papillomavirus (HPV), herpes simplex virus (HSV), Epstein-Barr virus (EBV), human cytomegalovirus (HCMV), and hepatitis C virus (HCV). ^{11 –14} In another study, Polansky et al suggested that the possible broad antiviral effects of Gene-Eden-VIR/Novirin may be mediated through the treatment’s effect on the immune system. ¹⁵

In the next section, we review evidence on the effects of the Gene-Eden-VIR/Novirin ingredients on the betacoronaviruses family of viruses, and specifically, the SARS-CoV virus.

Quercetin

Quercetin is a flavonol with a variety of biological effects, including antioxidant, anti-inflammatory, and antiviral. ^16,17 It has anti-infective and anti-replicative effects on a number of viruses, including RNA viruses. ^{16 –19} Studies showed that micromolar doses of quercetin can inhibit betacoronavirus infectious activities in vitro. One study reported that quercetin blocked pseudotype SARS-CoV entry into host cells (EC₅₀ = 83.2 μM). ²⁰ Two other studies observed that quercetin specifically inhibited the 2 SARS-CoV proteases, PLpro (IC₅₀ = 8.6 μM ²¹ ) and 3CLpro (IC₅₀ = 52.7 μM, ²¹ 73 μM ²² ), and the Middle Eastern Respiratory Syndrome protease 3CLpro (IC₅₀ = 34.8 μM ²¹ ). In addition, quercetin’s anti-inflammatory properties may have beneficial effects in respiratory viral infections, including CoV. ^23,24 Studies suggested that quercetin can modulate the cytokine release pattern associated with hyperinflammation and cytokine storm, ²³ while upregulating the proliferation of regulatory T helper cells. ²⁴

Green Tea

Green tea is made of leaves from the plant Camellia sinensis in a process that allows the preservation of certain flavonols commonly known as catechins. ²⁵ Several papers suggested that catechins have broad antiviral effects against many viruses. ²⁶ With regard to betacoronaviruses, one of the main catechins in green tea is epigallocatechin gallate (EGCG). This catechin was found to induce mild inhibitory effects on SARS-CoV 3CLpro (IC₅₀ = 73 μM) in vitro. ²²

Cinnamon

Cinnamon extract is most commonly derived from the species Cinnamomum cassia. Studies demonstrated that the plant has inhibitory effects on RNA viral infections in vitro. ^27,28 Zhuang et al also showed that a cinnamon extract inhibited an infection with the wild type SARS-CoV in vitro (IC₅₀ = 43 μM). ²⁹ The proposed possible mechanism was blocking cell entry via endocytosis.

Licorice

Licorice extract, derived from the root of Glycyrrhiza glabra, has broad antiviral ³⁰ and immunostimulating effects. In vitro ³¹ and human studies ³² showed that licorice stimulates the proliferation and activation of the human lymphocytes CD4+, CD8+, B cells, and NK cells. Reports from CoV patients indicate the involvement of this type of immune cells prior to the resolution of the disease, while overaccumulation of innate immunity cells, such as macrophages and neutrophils, at the site of infection, was associated with severe cases and death. ^33,34 Thus, licorice may promote early adaptive immunity-mediated clearance of the virus and prevent hyperinflammation. In addition, studies demonstrated a direct weak anti-infective activity of licorice’s main active ingredient, glycyrrhizin, on SARS-CoV in vitro. ^35,36

Selenium

Selenium is a trace element involved in redox regulation. Its antioxidative effect is exerted through the incorporation as selenocysteine into a group of proteins called selenoproteins. ³⁷ Selenium deficiency increases the levels of reactive oxygen species and oxidative stress, which impairs the response of the immune system to viruses ^38,39 and increases the rate of mutation of RNA viruses. ^{37 –40} This impaired response may be manifested in several forms ^38,39 : decreased immune cells function, as a result of oxidative damage; decreased cell-mediated immunity; more severe and persistent inflammation of the lungs, as seen in influenza A virus (IAV) infection; and an imbalance in the proliferation of different T cell types, including T helper cells (Th1/Th2) ratio. The increase in viral rate of mutation coupled with the decrease in the immune response to the viral infection may increase virulence, as it increases the population size of quasispecies, and, as a result, gives rise to new more virulent strains. These new strains can become dominant and increase the pathogenicity of the infection. ⁴¹ Harthill ⁴² suggested that this mechanism, which has been observed with other RNA viruses in selenium-deficient mice models, also occurred in the SARS-CoV outbreak in 2002. It is interesting that the outbreak started in areas of low selenium soil in China, such as Wuhan city. It should be noted that excess selenium is also detrimental to health. Studies showed that supranutritional supplementation of selenium caused an imbalance in the proliferation profile of T cell types, and impaired immune response. ^39,43 Finally, studies showed that adequate levels of selenium supplementation to selenium-deficient patients increased the immune response to viral infections, and decreased the virulence of several viruses, in some cases to the point of complete prevention of the disease. ^{37 –40}

Summary

In this article, we describe the effects of Gene-Eden-VIR/Novirin ingredients on the family of betacoronaviruses, and specifically SARS-CoV. We chose SARS-CoV because of its high level of sequence identity to the SARS-CoV-2 virus. We show that Gene-Eden-VIR/Novirin ingredients have anti-coronavirus effects, including inhibition of cell entry and infection, inhibition of replication, inhibition of the viral proteases, and reducing virulent quasispecies formation. In addition, different ingredients of Gene-Eden-VIR/Novirin may have positive effects on the response of the immune system to the SARS-CoV-2 virus by reducing detrimental hyperinflammation and increasing the function of specific immune components crucial for effective clearance of the virus. Importantly, a treatment approach that controls viral loads, while attenuating excessive inflammatory response, has been suggested as beneficial in CoV infections. We consider this evidence as a first indication of the anti-coronavirus effects of Gene-Eden-VIR/Novirin. Next, we are planning to conduct a clinical study with users of the treatments to test the effects of Gene-Eden-VIR/Novirin on the SARS-CoV-2 virus.